Iron deprivation of HL-60 cells with deferoxamine B mesylate (DFO) induced apoptosis. DNA fragmentation became apparent with 10Wh M DFO after 48 h treatment. The apoptosis peak according to the DNA histogram on flow cytometory and typical nuclear collapse and were observed microscopically after 48 h treatment with low4 M DFO. Cells treated with 10e4 M DFO for as little as 24 h were shown to be committed to apoptosis, as chromatin condensation progressed gradually thereafter.

Emphysematous gastritis is an extremely rare disease with an unfavorable prognosis. To date, very few studies have been conducted regarding the intragastric recovery process based on endoscopic findings. We herein report a case of emphysematous gastritis that improved with long-term (five months) conservative treatment in which we were able to observe the intragastric recovery process endoscopically. In cases in which emphysematous gastritis is suspected, it is important to provide prompt diagnostic imaging (including CT) and early appropriate treatment in order to improve the prognosis.

Background Peroral endoscopic myotomy (POEM) for achalasia is technically challenging to carry out in patients with type III, multiple prior treatments, prior myotomy, and sigmoid type. Herein, we present a series of consecutive patients with complex achalasia and introduce the POEM difficulty score (PDS). Aim To demonstrate the application and discuss the utility of PDS and present the feasibility, safety, and efficacy of POEM in complex achalasia patients. Methods Forty consecutive POEM were carried out with 28 meeting the criteria for complex achalasia. Primary outcome was clinical success (Eckardt score ≤3) at a minimum of 3 months follow‐up. Secondary outcomes included adverse events, procedural velocity and PDS. Results Twenty‐eight complex and 12 non‐complex POEM procedures were carried out with 100% and 92% clinical success, respectively, without any major adverse events with a median follow up of 15 months (complex) and 8 months (non‐complex). Mean velocities for non‐complex, type III, prior myotomy, ≥4 procedures and sigmoid type were as follows: 4.4 ± 1.6, 4.8 ± 1.5, 5.9 ± 2.2, 6.9 ± 2.2 and 8.2 ± 3.2 min/cm, respectively. Median PDS for non‐complex, type III, prior myotomy, ≥4 treatments and sigmoid type were 1 (0–3), 2 (0–4), 2.5 (1–6), 3 (2–6) and 3.5 (1–6), respectively. PDS was shown to correlate well with procedural velocity with a correlation coefficient of 0.772 (Spearman's P < 0.001). Conclusions PDS identifies the factors that contribute to challenging POEM procedures and correlates well with procedural velocity. The order of increasing difficulty of POEM in complex achalasia appears to be type III, prior myotomy, ≥4 treatments and sigmoid type.

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Expression of the cyclin kinase inhibitor, p21, is regulated both transcriptionally and posttranscriptionally by the ubiquitin-proteasome degradation pathway. Recently, we reported that DNA damage is required for efficient p21 expression by demonstrating that enhanced p21 mRNA expression induced by DNA damage results in increased p21 protein, but enhanced p21 mRNA without DNA damage does not. In addition, we demonstrated that DNA damage suppressed the ubiquitination of p21. In this study, we analyze the link between p21 stabilization and DNA damage. Enhanced p21 protein expression in ML-1 cells resulting from 15 Gy gamma-irradiation was diminished by Wortmannin or LY294002 pretreatment of cells. However, the levels of p21 mRNA were not affected by inhibitor pretreatment. Wortmannin or LY294002 pretreatment reduces p53 expression after gamma-irradiation to a lesser degree than that of p21. In addition, we examined the involvement of DNA-PK, whose activity is inhibited by Wortmannin or LY294002, in p21 stabilization using the SCID fibroblast cell line and a DNA-PK targeting ML-1 cell line. Accumulation of p21 protein by gamma-irradiation was similar to that of DNA-PK intact cells and was reduced by Wortmannin or LY294002 pretreatment. Involvement of another DNA damage detecting enzyme, the ATM gene product, whose activity is also inhibited by Wortmannin or LY294002, was evaluated. ATM deficient cells induced p21 after gamma-irradiation, gamma-irradiation-induced p21 protein was diminished by pretreatment of cells with Wortmannin or LY294002. We conclude that the p21 stabilization mechanism functions after gamma-irradiation, was sensitive to Wortmannin or LY294002, and required neither DNA-PK nor ATM gene product for activity.